Controlled initial surge despite high drug fraction and high solubility

Abstract

Potential connections between release profiles and solvent evaporation rates alongside polymer chemistry were elucidated for the release of tetracycline hydrochloride from two different poly (d, l-lactide-co-glycolide) (PLGA) film matrices containing high drug fractions (50%, 30%, and 15%), and prepared at two distinct solvent evaporation rates. At highest tetracycline concentrations (50%), (i) the early release rates were ≤0.5 μg/min in all cases; (ii) release was linear from systems fabricated with lower lactic content and slower solvent evaporation rate and bimodal from systems fabricated with higher lactic content and faster evaporation rate; (iii) surface fractions covered by the drug were similar at both evaporation rates for 85:15 PLGA but very different for 50:50 PLGA, leading to unexpectedly reduced early release from 50:50 PLGA than from 85:15 PLGA when both the matrices were fabricated using a slower evaporation rate. These features remained unaffected in case of low drug concentration. Results suggested that during the formation of the drug-polymer microstructure, the combined effect of polymer chemistry and solvent evaporation rate sets apart the surface characteristics and the initial release profiles of systems containing high drug fraction, and an appropriate combination of these parameters may be utilized to control the early stage of drug release.

• Biodegradable
• controlled release
• PLGA
• solvent casting
• solvent evaporation
• tetracycline

Acknowledgements

The authors thank Ms. Deidra Johnson, our former student intern at FDA, for helping with the initial elution experiments; and Dr. Kenya A. Brothers of the Office of Device Evaluation for valuable discussions at the early stage of the manuscript development.

Declaration of interest

The mention of commercial products, their source, or their use in connection with the material reported herein, is not to be construed either as an actual or implied endorsement by the Department of Health and Human Services.